Abstract Protein aggregation of neurotoxic proteins is a hallmark of Alzheimer?s disease (AD) and related dementias. In AD both the beta-amyloid (Ab) and tau proteins aggregate, and this protein aggregation is thought to be neurotoxic. One potential therapy for AD and related dementias is the development of strategies to reduce the levels of Ab and tau aggregation. Interestingly, we and others have found that one organism, Dictyostelium discoideum, is naturally resist to aggregation of another aggregation-prone protein that causes neurodegeneration. Further work from our laboratory has identified a novel molecular chaperone we named serine rich chaperone protein 1 (SRCP1) that is both necessary for Dictyostelium?s resistance to protein aggregation and sufficient to impart resistance to protein aggregation to other organisms. In this supplement we propose to: 1) determine if Dictyostelium is resistant to the aggregation of proteins that cause AD; and 2) determine if SRCP1 imparts resistance to protein aggregation and neuronal degeneration in a mouse model of AD. Together these studies will determine if Dictyostelium is a potential model for identifying proteins and pathways that suppress protein aggregation in AD and may lead to the development of novel therapeutics.